A5048181198- Extracellular vesicles in disease
- Cell Adhesion Molecules Research
- Osteoarthritis Treatment and Mechanisms
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Fatty Acid Research and Health
- Cytokine Signaling Pathways and Interactions
- Protease and Inhibitor Mechanisms
- Bone and Joint Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- Immune cells in cancer
- RNA modifications and cancer
- Knee injuries and reconstruction techniques
- Diabetes and associated disorders
- Blood properties and coagulation
- Immunotherapy and Immune Responses
- Pharmacology and Obesity Treatment
- Inflammatory mediators and NSAID effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Plant-Derived Bioactive Compounds
- Tendon Structure and Treatment
- Muscle metabolism and nutrition
- Asthma and respiratory diseases
William Harvey Research Institute
2013-2019
Queen Mary University of London
2013-2019
University of Birmingham
2012
University of Bristol
2012
Versus Arthritis
2012
University of Manchester
2012
Accumulation of lactate in the tissue microenvironment is a feature both inflammatory disease and cancer. Here, we assess response immune cells to context chronic inflammation. We report that accumulation inflamed contributes upregulation transporter SLC5A12 by human CD4+ T cells. SLC5A12-mediated uptake into induces reshaping their effector phenotype, resulting increased IL17 production via nuclear PKM2/STAT3 enhanced fatty acid synthesis. It also leads cell retention as consequence reduced...
Neutrophils generate chrondroprotective AnxA1-containing microvesicles that enter immune cell–impenetrable cartilage.
Abstract Interest in extracellular vesicle biology has exploded the past decade, since these microstructures seem endowed with multiple roles, from blood coagulation to inter-cellular communication pathophysiology. In order for microparticle research evolve as a preclinical and clinical tool, accurate quantification of levels is fundamental requirement, but their size complexity sample fluids present major technical challenges. Flow cytometry commonly used, suffers low sensitivity accuracy....
Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling arthritic joints from omega-3 supplemented mice identified elevated levels specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling human RA fluid revealed physiological RvD1, which — once applied to neutrophils attenuated chemotaxis. These results prompted analyses antiarthritic...
Bacterial-associated LPS drives oncostatin M–dependent airway inflammation and mucus hypersecretion in severe asthma.
Neutrophil activation and adhesion must be tightly controlled to prevent complications associated with excessive inflammatory responses. The role of the anti‐inflammatory peptide chemerin15 (C15) receptor ChemR23 in neutrophil physiology is unknown. Here, we report that expressed granules rapidly upregulated upon activation. C15 inhibits integrin clustering, reducing chemotaxis vitro . In inflamed microvasculature, modulates inducing adherent cell detachment from endothelium, while...
We hypothesized that exudates collected at the beginning of resolution phase inflammation might be enriched for tissue protective molecules; thus an integrated cellular and molecular approach was applied to identify novel chondroprotective bioactions. Exudates were 6 h (inflammatory) 24 (resolving) following carrageenan-induced pleurisy in rats. The resolving exudate subjected gel filtration chromatography followed by proteomics, identifying 61 proteins. Fractions added C28/I2 chondrocytes,...
<h3>Introduction</h3> Matrix metalloproteinase-14 (MMP14) plays an important role in atherosclerosis and angiogenesis. There is evidence indicating that hypoxia inflammatory stimuli up-regulate MMP14 expression whereas statins have opposite effect. However, the molecular mechanism by which these factors modulate unclear. We sought to investigate whether it involves transcription factor hypoxia-inducible factor-1 (HIF1). <h3>Methods Results</h3> A bioinformatics analysis of <i>MMP14</i> gene...
Argonaute (AGO) proteins execute microRNA (miRNA)-mediated gene silencing. However, it is unclear whether all 4 mammalian AGO (AGO1, AGO2, AGO3, and AGO4) are required for miRNA activity. We generate Ago1, Ago3, Ago4-deficient mice (Ago134Δ) find AGO1/3/4 to be redundant biogenesis, homeostasis, or function, a role that carried out by AGO2. Instead, regulate the expansion of type 2 immunity via precursor mRNA splicing in CD4+ T helper (Th) lymphocytes. Gain- loss-of-function experiments...
Dietary supplementation with omega‐3 PUFA is efficacious in reducing joint pain, morning stiffness and NSAID usage rheumatoid arthritis patients. Yet there an unmet need to determine how they exert beneficial effects. Recent discoveries have determined that can be enzymatically converted vivo novel pro‐resolving bioactive lipid mediators, termed resolvins. We recently showed resolvin D1 (RvD1) limits PMN recruitment experimental peritonitis via its receptor ALX (PMID:22499990), yet whether...
Microparticles (MPs), subcellular vesicles released from most eukaryotic cells, play important roles in inflammation. We found abundant endogenous neutrophil MPs present rheumatoid arthritis (RA) synovial fluid compared to paired plasma analyses. These were highly enriched Annexin A1 (AnxA1), a potent anti‐inflammatory protein. Addition of vitro generated AnxA1 +ve IL‐1‐stimulated 3D chondrocyte cultures, rodent cartilage explants, or injected intra‐articularly model inflammatory arthritis,...
Microvesicles (MVs) mediate inter‐cellular communication by transferring cellular components to target cells, endowing them with an enhanced lipid and protein repertoire. We aimed determine the function of neutrophil‐derived MVs in arthritis, as their concentration was augmented synovial fluid rheumatoid arthritis patients compared paired plasma. Neutrophils adoptively‐transferred into arthritic mice migrated inflamed joints released MVs, observed abundantly within cartilage; first evidence...
Microparticles (MPs) are small membrane‐bound vesicles released by cells upon activation. Numerous reports have detected MPs in the synovial fluid of Rheumatoid Arthritis (RA) patients. Whilst Tcell‐ derived activate synoviocytes, recent shed light on possible anti‐inflammatory phenotype neutrophilderived MPs, challenging linear model inflammation. The aim study is to unveil role neutrophil‐derived RA, particularly context cartilage biology. generated from human neutrophils were...
<h3>Background</h3> Chemotherapies are first-line cancer treatments, often preceding immunotherapies, but their impacts on immune responses poorly understood. Drug discovery pipelines typically must choose between large library screens with simple readouts or small, targeted compound sets for more complex mechanistic investigation. Spring's Immune Compass<b> uses machine learning (ML</b><b>) analyses of high-content cell paint images and secreted protein profiles to simultaneously screen...
Introduction The resolution of inflammation is a process that ensures repair and restoration tissue physiology. Using integrated approach with proteomic analyses bio‐assays human chondrocytes experimental arthritis, we identified α 1 ‐Antitrypsin(AAT), the chief neutrophil elastase(NE) inhibitor, as novel chondroprotective protein produced in resolving exudates. Methods Resolving rat pleural exudates (24h post‐carrageenan injection) were run for mass spectrometry using ion‐trap analyzer...